WO2002092112A1

WO2002092112A1 - Oral supplement

Info

Publication number: WO2002092112A1
Application number: PCT/GB2002/002056
Authority: WO
Inventors: Patrick Holford
Original assignee: Holford and Associates Ltd
Current assignee: Holford and Associates Ltd
Priority date: 2001-05-11
Filing date: 2002-05-03
Publication date: 2002-11-21
Anticipated expiration: 2003-11-11
Also published as: GB0111579D0

Abstract

The present invention relates to an oral supplement comprising three or more of kava kava, sceletium, S-adenosyl methionine or a precursor therefor, and 5-hydroxytryptophan or a precursor therefor. In addition, the invention relates to the oral supplement which further comprises B vitamins. The invention also relates to a composition comprising three or more of kava kava, sceletium, S-adenosyl methionine or a precursor therefor, and 5-hydroxytryptophan or a precursor therefor for use in increasing relaxation of a subject, improving the mood of a subject and/or for making the subject feel more light hearted and humorous.

Description

Oral Supplement

The present invention relates to an oral supplement comprising three or more of kava kava, sceletium, S-adenosyl methionine or a precursor therefor, and 5-hydroxytryptophan or a precursor therefor. In addition, the invention relates to the oral supplement which further comprises B vitamins. The invention also relates to a composition comprising three or more of kava kava, sceletium, S-adenosyl methionine or a precursor therefor, and 5-hydroxytryptophan or a precursor therefor for use in increasing relaxation of a subject, improving the mood of a subject and/or for making the subject feel more light hearted and humorous. The invention further relates to the use of three or more of kava kava, sceletium, S-adenosyl methionine or a precursor therefor, and 5-hydroxytryptophan or a precursor therefor in the manufacture of compositions for increasing the relaxation of a subject, for improving the mood of a subject and/or for making a subject feel more light hearted and humorous. Furthermore, the invention relates to a method of increasing the relaxation of a subject, for improving the mood of a subject and/or for making a subject feel more light hearted and humorous, the method comprising administering to the subject three or more of kava kava, sceletium, S-adenosyl methionine or a precursor therefor, and 5- hydroxytryptophan or a precursor therefor according to the invention. The invention also relates to a foodstuff comprising three or more of kava kava, sceletium, S- adenosyl methionine or a precursor therefor, and 5-hydroxytryptophan or a precursor therefor.

Dimethyl tryptamine (DMT) is closely related to the neurotransmitter serotonin and is thought to act much like a neurotransmitter. It is believed to be produced primarily in the pineal gland, along with serotonin and melatonin. The pineal gland is light sensitive in many animals and is necessary for them to be connected to the environment and the ebb and flow of day and night, as well as seasonal changes. It has been found that entheogens have profound effects on the neurotransmitter serotonin and, perhaps most importantly, on DMT. However, almost all entheogens that stimulate the release of or mimic the effects of a neurotransmitter generally lead to a state of imbalance known as "down regulation", which creates a state of deficiency and hence craving.

DMT is understood to be produced through methylation of tryptamine by S-adenosyl methionine. The tryptamine is produced from tryptophan. The tryptophan may also be converted into 5-hydroxytryptophan which is an effective precursor for serotonin. Accordingly, the amino acid tryptophan, which is a normal constituent of food, is a basic building block not only of serotonin, but also of tryptamines, such as DMT. Indeed, tryptophan deficiency leads to depression, while supplementing tryptophan has proven an effective anti-depressant. However, tryptophan is not generally available as a supplement.

5-hydroxytryptophan (5-HTP) occurs naturally in an African plant, Griff onia simplifica and is known to produce an improvement in patients showing the symptoms of depression, anxiety or insomnia.

S-adenosyl methionine is naturally occurring and donates methyl groups in the manufacture of neurotransmitters. It therefore has an important role in the production of a wide range of brain chemicals such as DMT and serotonin. S-adenosyl methionine has been shown to be effective as an anti-depressant. However, it is relatively unstable and is also expensive. The body can make S-adenosyl methionine from trimethylglycine (TMG), which is stable and also less expensive than S-adenosyl methionine. TMG can be extracted from sugarbeet and is also found in broccoli and spinach. The production of S-adenosyl methionine from TMG also yields dimethylglycine. B vitamins are known to be co-factors for making neurotransmitters. For some enzymes involved in the production of the neurotransmitters vitamins B3, B6, B12 or folic acid may be required. Deficiency of any one of these is associated with depression, mental illness, schizophrenia and unpleasant hallucinations. Supplementing these has a reverse effect, and has been shown to dramatically improve a patient's mental and emotional well being.

Sceletium is a native South African creeper, also called kougoed, which has been used by hunter-gatherer tribes since prehistoric times. It lessens anxiety, stress and tension and raises spirits. If taken in a very large dose the subject may even feel euphoric, then taken over by a sense of drowsiness. It does not cause hallucinations. Nor do nearly 400 years of documented use reveal many serious adverse effects, either.

Traditionally, sceletium is chewed, brewed as a tea, or used as snuff. If enough is chewed, it has a mild anaesthetic effect in the mouth, much like kava kava, and is used by the San people of South Africa for tooth extractions, or is given in minute doses to children with colic. A tea made from sceletium is used to wean alcoholics off their tipple. In this way the recovering alcoholic can avoid withdrawal symptoms.

People have reported that sceletium-induced relaxation has helped them to focus on inner thoughts and feelings, or to have a heightened experience of the beauty of nature. Some have reported an increased sensitivity of the skin as well as sexual arousal, while other subjects have said it leaves them feeling free of fear and stress.

The active constituents of the plant are alkaloids, including mesembrine, mesembrone, mesembrenol and tortuosamine. It is thought that its major alkaloid, mesembrine, acts as a serotonin-uptake inhibitor thereby helping to keep more serotonin in circulation. It also appears to have a harmonising and balancing effect on other neurotransmitters associated with motivation - dopamine and noradrenalin, as well as adrenalin. Kava kava is known to enhance GABA activity, the relaxing neurotransmitter that also modulates dopamine, adrenalin and noradrenalin. Accordingly, kava kava is able to cause relaxation of muscles and is an effective anti-anxiety agent. Kava kava contains kavalactones and is known as a relaxing supplement.

A number of references discuss each of kava kava, sceletium, S-adenosyl methionine, trimethylglycine, 5-hydroxytryptophan, tryptophan and B vitamins. These are Volz, H & Kieser, M. Kava Kava Extract WS 1490 versus Placebo in Anxiety Disorders - A randomised Placebo-Controlled 25-Week Outpatient Trial, Pharmacopsychiat, 1997, 30: 1-5;

E Lemart, "Secular Use of Kava in Tonga", Quarterly Journal of Studies on Alcohol, vol 18(1967), pp 328-41;

M Smith et al , "Psychoactive constituents of the genus sceletium: a review", Journal of Ethnopharmacology, vol 50, no. 3 (1996), pp 119-30;

Ecclestone, D (1993). L-tryptophan and depressive illness: a valuable adjunct to therapy? Psychiatric Bulletin, 17, 223-224;

K A Smith et al (1997) "Relapse of depression after rapid depletion of tryptophan", Lancet, vol 349, pp 915-19;

Poldinger, et al (1991). A functional-dimensional approach to depression: serotonin deficiency and target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology, 24, 53-81;

G M Bressa, "S-adenosyl methionine as antidepressant: meta-analysis of clinical studies", Acta Neurologica Scandanavian Supplement, vol 154 (1994), pp 7-14; P S Godfrey et al , "Enhancement of recovery from psychiatric illness by methylfolate", Lancet, vol 336 (1990), pp 392-5;

A Hoffer, H Osmond et al , "Treatment of schizophrenia with nicotinic acid and nicotinamide", Journal of Clinical Experimental Psychopathology, vol 18 (1957), pp 131-58;

C Pfeiffer et al , "Treatment of pyroluric schizophrenia with large doses of pyridoxine and zinc", Journal of Orthomolecular Psychiatry, vol 3 (1974), pp 292-3; and C Pfeiffer et al , "Copper, zinc, manganese, niacin and pyridoxine in the schizophrenias", Journal of Applied Nutrition, vol 27 (1975), pp 9-39.

In the present specification, the terms sceletium and kava kava are also intended to include one or more respective active components thereof.

According to a first aspect of the present invention there is provided an oral supplement comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor and S-adenosyl methionine or a precursor therefor.

Kava kava which desirably contains between approximately 15% and 40% kavalactones may be provided as a standardised extract or as a liquid. The amount of kava kava is preferably in the range of 50mg to 1200mg. More preferably, 250mg to 500mg is provided.

Sceletium, which contains mesembrine, mesembrenone, mesembranol and tortuosamine, is desirably present in the oral supplement in an amount of between lOmg to 300mg. More preferably, the sceletium is provided in an amount of lOOmg to 200mg. The S-adenosyl methionine is desirably in the form of tosylate or butanedisulfonate and is in an amount of between 25mg to 750mg. The precursor is desirably trimethylglycine which is desirably present in the oral supplement in an amount of between lOOmg to 2000mg.

5-hydroxytryptophan may be obtained from Griffonia simplifica or may be synthetically produced. Preferably the 5-hydroxytryptophan is present in the oral supplement in an amount of between lOmg to 300mg. The precursor for 5-hydroxytryptophan may be tryptophan and is present in an amount of 50mg to 2000mg in the oral supplement.

The supplement may also comprise one or more B vitamins. Such B vitamins may include one or more of niacin (vitamin B3), panto thenic acid (vitamin B5), folic acid, vitamin Bl, B2, B6 and B12. The niacin may be in the form of nicotinamide or nicotinic acid. As noted above, such B vitamins are known to act as co-factors in the production of neurotransmitters in the brain. The level of B vitamins is not limiting. A preferred total range is from approximately 80mg to 250mg.

The preferred ranges of each of the components of a preferred oral supplement dose are provided in the table below.

In addition, preferred levels of other components may be as follows:

Such an oral supplement may be provided in the form of capsule or tablet, or even a liquid or powder. The oral supplement may be taken alone or may be added to foodstuffs.

The combination of the above mentioned components of the oral supplement demonstrates significant effects to a human subject. Such effects may include one or more of increased alertness, increased clarity of thought, sharper vision and reduced appetite as well as increased relaxation. Alternatively or in addition, the subject may feel more light-hearted or humorous. Furthermore, the mood and creativity of the subject may also be improved on using the oral supplement. Use of the oral supplement with alcohol may result in decreased drowsiness associated with alcohol and may also decrease the short-term effects of alcohol on a subject. In addition, the subject's motor skills may be better than if alcohol alone was taken. The oral supplement may also have the effect of increasing a subject's sexual enjoyment.

In a second aspect of the present invention there is provided a composition comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and 5-adenosyl methionine or a precursor therefor, for use in increasing relaxation of a subject. The composition may be, for example, in the form of an oral supplement, a medicament or foodstuff. In a third aspect of the present invention there is provided a composition comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and 5-adenosyl methionine or a precursor therefor, for use in improving the mood of a subject. The composition may be, for example, in the form of an oral supplement, a medicament or foodstuff.

In a fourth aspect of the present invention there is provided a composition comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and 5-adenosyl methionine or a precursor therefor, for use in making a subject feel more light-hearted. The composition may be, for example, in the form of an oral supplement, a medicament or foodstuff.

In a fifth aspect of the present invention there is provided a composition comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and 5-adenosyl methionine or a precursor therefor, for use in making a subject feel more humorous. The composition may be, for example, in the form of an oral supplement, a medicament or foodstuff.

Accordingly, in a sixth aspect of the present invention there is provided the use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for increasing relaxation of a subject. The composition may be, for example, in the form of an oral supplement, medicament or foodstuff.

In a seventh aspect there is provided the use of three or more of kava kava, sceletium,

5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for improving the mood of a subject. The composition may be, for example, in the form of an oral supplement, a medicament or foodstuff. In addition, in an eighth aspect there is provided the use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for making a subject feel more light-hearted. The composition may be, for example, in the form of an oral supplement, a medicament or foodstuff.

In addition, in a ninth aspect there is provided the use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for making a subject feel more humorous. The composition may be, for example, in the form of an oral supplement, a medicament or a foodstuff.

There is also provided in a tenth aspect a method of increasing the relaxation of a subject, the method comprising administering to a subject in need thereof three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S- adenosyl methionine or a precursor therefor.

The invention may further relate in an eleventh aspect to a method of improving the mood of a subject the method comprising administering to a subject in need thereof three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

Furthermore, the invention relates in a twelfth aspect to a method of making a subject feel more light-hearted comprising administering to the subject in need thereof three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and

S-adenosyl methionine or a precursor therefor.

In a thirteenth aspect the invention relates to a method of making a subject feel more humorous comprising administering to the subject in need thereof three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

In accordance with the invention, the subject is preferably a human. The human may be over the age of 16 years, 18 years or 21 years.

The invention may further provide in a fourteenth aspect a foodstuff which comprises three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

The foodstuff is preferably in the form of a liquid, which liquid may be a drink. Alternatively, the foodstuff may be in the form of baked goods or ready to eat cereal.

In the above aspects the kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor may be provided for simultaneous, separate or sequential use. For example, the kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor may be provided as individual oral supplements in separate containers. Alternatively at least two of the components may be provided in the same container (as individual oral supplements or combined). The containers may be packaged together (for example a pack of three or more containers, each containing one of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor and S-adenosine methionine or a precursor therefor).

The preferred features of the first aspect apply to each of the second to fourteenth aspects mutatis mutandis.

The invention will now be described by way of example only and with reference to the following examples. Examples

Responses to the individual compounds kava kava, sceletium, tryptophan or its precursor 5-hydroxytryptophan (5-HTP), 5-adenosyl methionine (SAMe) or its precursor trimethylglycine (TMG) have been reported in the scientific literature, with the exception of sceletium for which there are limited reports. These reports indicate that SAMe or TMG (which is a precursor for SAMe) on its own has a mild, often imperceptible stimulant effect, subtly improving alertness. 5-HTP or tryptophan (which is a precursor for 5-HTP) has an anti-depressant effect which is generally imperceptible in those who are not depressed. Kava kava, on its own, has a mind relaxing, muscle relaxing and mood improving effect, usually occurring with doses above 150mg of kavalactones, which is equivalent to 500mg of a standardised extract containing 30 per cent kavalactones.

Sceletium was tested on 5 volunteers in doses of lOOmg to 300mg. Responses ranged from nothing to feeling clear headed and a sense of expansion.

The effects of these nutrients and herbs in combination was investigated. It was found that kava kava and 5-HTP or SAMe were not perceptibly different to kava kava alone. Sceletium and 5-HTP or SAMe were not perceptibly different to sceletium alone.

SAMe and 5-HTP had no significant effect. Kava kava and sceletium produced a mild increase in alertness and mental clarity. With alcohol this induced a deeper than usual sense of relaxation. Kava kava, sceletium and SAMe produced a much more noticeable increase in alertness, mood and an overall sense of well-being. Kava kava, sceletium, and 5-HTP produced a much more noticeable increase in alertness, mood and an overall sense of well-being. Sceletium, SAMe and 5-HTP produced a much more noticeable increase in alertness, mood and an overall sense of well-being. Finally, kava kava, sceletium, TMG and 5-HTP produced the most significant improvement in mood, relaxation, light-heartedness, clarity of mind and well-being. It therefore appeared that there was a synergistic effect, which becomes apparent with the combination of at least three of these nutrients and herbs (kava kava, sceletium, TMG/SAMe and 5-HTP). The effects of all four ingredients were then tested more thoroughly on a group of 20 volunteers.

The ingredients were provided in the following amounts in an oral supplement of two capsules, taken once, twice or three times over the course of an evening.

Ingredient Amount

Kava kava extract 400mg

Sceletium powder lOOmg

TMG 600mg

5-HTP 50mg

Pantothenic acid (Vit B5) lOOmg

Niacin (as nicotinamide) (Vit B3) 30mg

Niacin (as nicotinic acid) (Vil B3) lOmg

Vit B6 20mg

Vit B12 lOμg

Folic acid lOOμg

The vitamins are included as they are known to be co-factors for making neurotransmitters and as such may improve the effect of the kava kava, sceletium, TMG and 5-HTP.

20 people were given the oral supplement in capsules or in a drink. Participants were asked to complete a questionnaire and to give their comment on the effects of what they took. The results were:-

Therefore :-

85%) had improved mood

85% felt they were more light-hearted and humorous

80%) felt more alert

70% felt more relaxed

65%o felt their vision was sharper

60%) felt their thinking was clearer

55% felt more creative

50%) felt their appetite was reduced Of those that responded (18) 89% had no negative effects 100%) said they would take in again.

In addition 10 volunteers took the oral supplement with small amounts of alcohol.

NEXT DAY hungover (bad, mild, no 10 (no) hangover)

NEXT DAY more alert or awake

NEXT DAY more energy 5, 1 less energy

NEXT DAY more creative 3

NEXT DAY improved/worsened mood 10

Of the volunteers that responded:-

80% felt they needed less alcohol

60%) felt less drowsy than they would expect on alcohol alone

75% felt more awake and energised than they would expect on alcohol alone

44% felt their motor skills were better, 44% no difference, 11% worse

71%) felt better the next day than they would on alcohol alone

None reported having a hangover and all reported having improved mood. Some volunteers repeated the "active dose" of 2 capsules to a maximum of six capsules during the course of the evening. This had the reported effect of prolonging the beneficial effects.

In these investigations, the following comments were made by the volunteers:-

"The effects were pretty instant. Really nice. A very pleasant experience. My quality of sleep seemed better."

"Time is altered. There is more light. Everything is sharper. I found it interesting and enjoyable. Noticed an improved sense of touch."

"Top of the head feels expanded."

"For a few hours I felt very relaxed, and nothing bothered me. I'm quite stressed at present so this was quite a pleasant experience."

"I was on the tube, I was waiting at the airport, I was on the plane, and as I ^■ looked around I was still really high! I felt a real sense of lovingness towards the world and my fellow man- woman."

"Feels like that warm, mellow, relaxing feeling after 2 glasses of wine, but I'm more awake.

"My evening was spent listening to music and dancing and feeling ... as good as it gets ... in that realm. An electrical tingling that was physically in the brain. I was charged!"

"I noticed a clearing of my mind, no tiredness, a lifting of my consciousness." "Really enjoyed my 6 capsules and felt a warm, floaty, friendly, connected feeling - subtle but perceptible."

"I felt very mellow, expansive. Even after a couple of hours I felt clear and good and more gentle. It's like the edge of life was softened."

"There is no doubt that there is an enhanced state. It isn't the quick hit of a drink but there is a definite calming effect which builds almost imperceptibly and with no loss of function. After a couple of drinks I'm normally fading badly within an hour - this didn't do that to me. It gave a sense of well-being, the relaxing effect of a weak alcoholic drink without the associated dilution of control. A quietly expanded state which is gentle but powerful. I'm still up (yet relaxed!) 18 hours later and there is an unequivocal improvement in acuity, perception, enthusiasm, creativity and productivity. Today has been a very good day and it is no coincidence! It appears to enhance with fresh air, any exercise (even a walk to the car)."

"A positive experience. Most noticeable was the clarity of mind."

"Felt a real buzz for half an hour, then felt really chilled and 'out of this world' for half an hour. I love the fact that the supplement is natural. I drank less alcohol because it gave me a natural high."

"My best night in a club ever."

"Dulls any sort of anxiety but not enthusiasm."

"A mild and side-effect free enhancement of relaxation, enjoyment and intuition." "My worries evaporated."

"Light, uplifting and pleasant."

"I was impressed that it was like a caffeine high without the side-effects and it improved my mood as well. It made me more alert, happier and more energy without any unwanted side-effects."

"Had migraine prior to taking the supplement which usually finishes me off.

But I felt good and went out that evening and laughed all night."

Claims

1. An oral supplement comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and S-adenosyl methionine or precursor therefor.

2. An oral supplement as claimed in claim 1, wherein the precursor of S-adenosyl methionine is trimethylglycine.

3. An oral supplement as claimed in claims 1 or 2 wherein the precursor of

5-hydroxytryptophan is tryptophan.

4. An oral supplement as claimed in any of claims 1 to 3, wherein the supplement further comprises one or more B vitamin.

5. An oral supplement as claimed in claim 4, wherein the B vitamin is one or more of niacin, folic acid, panto thenic acid, Bl, B2, B6 and B12.

6. An oral supplement as claimed in any of the preceding claims, wherein the kava kava contains from 15 to 40% kavalactones.

7. An oral supplement as claimed in any of the preceding claims, wherein the sceletium contains mesembrine, mesembrone, mesembrenol and/or tortuosamine.

8. An oral supplement as claimed in any of the preceding claims, wherein the

5-hydroxytryptophan is obtained from Griffonia simplifica, and/or is synthetic.

9. An oral supplement as claimed in any of the preceding claims, wherein the S-adenosyl methionine is in the form of tosylate and/or butanedisulfonate.

10. An oral supplement dose as claimed in any of the preceding claims, which provides an amount of kava kava between 15mg to 1200mg.

11. An oral supplement dose as claimed in any of the preceding claims, which provides an amount of sceletium between lOmg and 300mg.

12. An oral supplement dose as claimed in any of the preceding claims, which provides an amount of 5-hydroxytryptophan between lOmg to 300mg.

13. An oral supplement dose as claimed in any of the preceding claims, which provides an amount of S-adenosyl methionine between 25mg to 750mg.

14. An oral supplement dose as claimed in claim 2 or any of claims 3 to 12 when dependent on claim 2, which provides an amount of trimethylglycine between lOOmg to 2000mg.

15. An oral supplement dose as claimed in claim 3 or any of claims 4 to 14 when dependent on claim 3, which provides an amount of tryptophan of between 50mg to 2000mg.

16. A composition comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and S-adenosyl methionine or a precursor therefor, for use in increasing the relaxation of a subject.

17. A composition comprising three or more of kava kava, sceletium,

5-hydroxytryptophan or a precursor therefor, and S-adenosyl methionine or a precursor therefor, for use in improving the mood of a subject.

18. A composition comprising three or more of kava kava, sceletium, 5-hydroxytryptophan or a precursor therefor, and S-adenosyl methionine or a precursor therefor, for use in making a subject feel more light-hearted.

19. A composition comprising three or more of kava kava, sceletium,

5-hydroxytryptophan or a precursor therefor, and S-adenosyl methionine or a precursor therefor, for use in making a subject feel more humorous.

20. Use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for increasing the relaxation of a subject.

21. Use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for improving the mood of a subject.

22. Use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for making a subject feel more light-hearted.

23. Use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor in the manufacture of a composition for making a subject feel more humorous.

24. A method of increasing the relaxation of a subject comprising administering to a subject three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

25. A method of improving the mood of a subject comprising administering to a subject three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

26. A method of making a subject feel more light-hearted comprising administering to a subject three or more of kava kava, sceletium, 5- hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

27. A method of making a subject feel more humorous comprising administering to a subject three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

28. A foodstuff comprising three or more of kava kava, sceletium, 5- hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor.

29. A foodstuff as claimed in claim 22, wherein the foodstuff is in the form of a liquid.

30. A foodstuff as claimed in claim 22, wherein the foodstuff is in the form of baked goods.

31. A composition, as claimed in any one of claims 16 to 19, or a foodstuff as claimed in any one of claims 28 to 30 having one or more of the features as set out for the oral supplement in claims 2 to 15.

32. Use, as claimed in any one of claims 20 to 23, having one or more of the features as set out for the oral supplement in claims 2 to 15.

33. A method, as claimed in any one of claims 24 to 27, having one or more of the features as set out for the oral supplement in claims 2 to 15.

34. An oral supplement substantially as hereinbefore described with reference to one or more of the examples.

35. A composition substantially as hereinbefore described with reference for one or more of the examples.

36. Use of three or more of kava kava, sceletium, 5-hydroxytryptophan, or a precursor therefor, and S-adenosyl methionine or a precursor therefor substantially as hereinbefore described with reference to one or more of the examples.

37. A foodstuff substantially as hereinbefore described with reference to one or more of the examples.