QUALITY CONTROL FOR SUPER-EXTRACTS
Quality control for conventional multi-herbal products is a major issue even now. This is because the levels of active metabolites are known to vary with the season. Many formulations contain more than 10 herbs. In addition, there is really no simple and effective method to define quality of the final poly-herbal composition containing more than 10 herbs.
ACTIVE INGREDIENTS UNKNOWN
The case of Super-extracts is even more complex .Most of the known active molecules in herbs are required at mg to tens of mg level for them to produce an effect. Super-extracts seem to work at mg level of the parent plant. Simple arithmetic makes it clear that therefore super-extracts must contain a new class of active molecules which must work at micro to nano gm levels. Almost all of the known drug molecules are monomers and are also needed in mg to tens of mg quantities. Recently, a lot of work is being done on oligomers (peptides and saccharides) and they are known to work at such micro and nano levels. It is therefore hypothesized (not proven) that the super-activity is a result of cell wall fragments coming in to the oil. Cell wall is made up of lipoproteins and liposaccharides. These will easily come into the oil phase during boiling and breakdown into fragments. Such fragments are likely to be oligomeric and therefore capable of super-activity.
However, identifying such fragments will require a massive research effort and although of considerable National and Global interest in the long term, cannot make for an affordable solution if needed to be done in each case by any individual firm. Without such a long term effort, it is impossible at present to develop any quality control method based on the chemical analysis of the active contents.
A SIMPLE SOLUTION WORKS
Where do we go from here?
Being aware of the likely seasonal variations of active plant metabolites, I made super-extracts of the first chosen herb in each month of the year. Dosage was fixed in terms of mg of parent plant. I did not find any significant change in activity with changing seasons. Since this is the only method available to me i.e. fix dosage on the basis of mg of herb, I have followed this method for all herbs over the past two decades. So far the mg basis seems to have worked.
A possible explanation perhaps rests with the hypothesis that it is the cell wall fragments which are super-active. It is reasonable to think that whereas the expressed cellular metabolite levels may change from season to season, the composition of the cell membrane will be much more invariant. This, in fact, may be the lucky break which has allowed mg based dosage to work all these years with a large number of herbs used in a wide variation of applications.
The use of a simple mg based method therefore is a workable method of quality control and can be easily handled even at the village level without the need for any sophistication.
Is it safe for any person to directly make and sue super-extracts? This is a natural question and the answer lies in the following considerations.
Conventional herbs and Simple cooking recipe: The herbs being used start with normal spices (Ginger, Pepper, Cumin, Garlic, Methi, Haldi) used in everyday cooking. The list also includes other herbs which are generally considered to be above suspicion (Amla, Brahmi, Aloe, Tulsi, Gulvel etc.). All other herbs are also those used routinely in Ayurveda.
The process is also a simple modification of the typical phodni / tadka process in everyday cooking. The total cooking time is typically 60 to 90 minutes.
The absolute dose is at least 100 times lower than conventional.
All of these factors should make it possible to accept that the super-extracts can be made directly by people themselves and there should really not be any concern about developing unexpected toxicity.
Such direct use without a very expensive proving and using a simple mg based dosage is the key element of Accessibility and Affordability.
The overall considerations that go into the safety benefits and side effects of herbal and biomass and metal based super-extracts are considered below in greater details.
1. Inherent Safety and Benefits of Low Absolute Dose: The absolute daily dose of any biomass or metal is reduced 100 to 1000 fold when they are administered in the form of super-extracts. Thus, in case of a typical herb, in place of a daily dose of 1 to 2 gm, only 5 to 10 mg may be sufficient in the form of a super-extract. This leads to the following benefits:
Reduction in Accumulation Toxicity: A number of herbs may be a rich source of fat soluble molecules such as steroids which can accumulate if the herb is given for long periods. A good example is the use of guggul (Commifora mukul) or herbs such as Shatavari(Asparagus racemosus). Since the dose in the form of super-extracts is reduced at least 100 fold, the accumulation, if any, is also reduced by that factor.
Dosages of any other toxic heavy metals or other toxic molecules picked up by the growing herbs from the soil are also reduced 100 to 1000 fold.
Another example is the use of metals. Bhasma such as Tamra Bhasma are given at a metal dose level of a few mg/day. There are a number of other nanocolloids of metals such as Gold, Silver, Copper and Zinc available in the market. The suggested dose is 15 ml of a 1liquid containing 10 ppm of metal as nanoparticles. This amounts to a metal dose of 150 mcg. In contrast, the metal super-extracts of Gold, Silver, Copper and Zinc seem to work at 100 mg/day of the oil containing 1 to 20 ppm of metal as nanoparticles. This is a metal dose of 0.1 to 2 mcg or at least 100 times lower than the conventional metal dose.
Efficient Nasal and Topical Absorption: Super-extracts produce very fast effects when given nasally. They also seem to produce fast effects when applied topically to the known chakra points such as the top of the crown, outside the nose, outside the ears where the trigeminal nerve comes out and so on. They also produce excellent results applied directly to cuts, abrasions and skin inflammations. In all these applications very low doses appear to be adequate.
These effects allow a considerable extension of application range with a very low dose levels.
Ease of Making and Administering Balanced Combinations: Ayurveda has always provided a balanced formulation which will simultaneously work to reduce the specific symptom but also work to protect and support the G.I. System, liver, kidney, heart and so on. However, conventional forms often require large quantities of herbs and also their decoctions. The palatability and the other timing requirements of such packages often lead to non-acceptance or poor compliance by patients. With super-extracts, palatability issues disappear due to low dosage and the administration is also much more patient-friendly.
Thus, the low absolute dose allows many inherently safe and efficient means of medicinal delivery.
2. Side Effects of Overdose: There is often a misconception that herbal medicines have no side effects. This is simply not true. As a general rule, any substance will produce undesirable biochemical effects in the human body as the dose is increased beyond a certain levels. To understand this it is useful to take a look at the widely different dose levels recommended for different medicinal plants and also the side effects of overdose as shown in Table 1. In this Table 1, the herbal materials are approximately classified into three categories depending on their dose levels.
Table 1: Recommended Dose Levels of Medicinal Plants and Known Side Effects
Source: Gogte V.M. “Ayurvedic Pharmacology & Therapeutic Uses of Medicinal Plants”. Translation:The Academic Team of Bharatiya Vidya Bhavan’s SPARC. 2000.
|Name of Natural product||Special Precautions||Conventional Dosage, per Day||Super-extract Dosage/Day|
|Type I – Poisons|
|Strycnos nux vomica
|Purified and given in Ghee. Excess causes convulsions||1 to 2 grain||Not Applicable (N.A.)|
|After purification, with milk / ghee.Only during winter and spring||1.5 mg Rhizome||N.A.|
|Type II – Strong Irritants|
|Plumbago zeylanica||Higher dose causes burning and intoxication||0.5 to 1 gm root bark||0.5 to 1 mg|
(Arka – Mandar)
|With milk / ghee. 2 to 5 gm causes stomach burning / vomiting||0.5 to 0.75 gm bark/latex|
|Purified and given with ghee. Overdose causes liver/lung toxicity. Also, vertigo, weight loss, impotency etc.||0.5 to 1.5 gm resin||0.5 to 1 mg|
|Higher dose leads to constipation||0.5 to 1 gm seed powder||3 to 7 mg|
|3 to 6 gm dose purgative||0.75 to 1 gm root powder||2 to 5 mg|
|0.25 to 0.5 gm – fruit|
|0.75 to 1.5 gm powder||2 to 5 mg|
|Type III – Adaptogens|
|1-3 gm bud paste||3 to 7 mg|
|1 to 3 gm bark powder||5 to 10 mg|
|3 to 5 gm powder||5 to 10 mg|
|3 to 6 gm powder||5 to 15 mg|
|10 to 20 ml juice||5 to 20 mg|
The above data brings out several points.
Type I plants are generally known as poisonous plants. Their useful dose is generally just a few mg / D or even a fraction of a mg / D. They have to usually go through a purification process and the overdose is definitely known to produce serious side effects.
Type II plants are still quite potent. They are generally used at the level of 1 gm / D. They also very definitely produce undesirable side effects at a dose 10 times more than the beneficial dose. These include a large number of spices (ginger, pepper) and several other routinely used medicinal herbs.
Type III plants typically include adaptogens (Rasayana herbs). They are used at the level of 5 gm /D. One does not often talk about side effects with these herbs. However, there is no doubt that a large overdose will produce undesirable effects even in this case.
Food materials are also not free from side effects at high doses for a long period of time. A few illustrative examples are given below.
Consider a few Ushna and Pittavardhak food items
– Safflower oil is one of the richest sources of w-6 fatty acids and is considered not only beneficial but essential. However, it is also known that a large excess of it will produce inflammatory eicosanoids and is therefore harmful.
– Flaxseed oil is a rich source of w-3 fat. According to Ayurveda, long term use of this in large quantities is harmful as it will be bad for eyesight. There is enough personal experience that an intake of even two teaspoons of flaxseed powder can produce burning in the eyes.
– Raw spouts are also regarded as a very good source of enzymes and vitamins. However, large amounts lead to over activation and can easily lead to eye burning, dryness of eyes and other undesirable long term consequences. Ayurveda provides a cautionary warning against the use of these in large amounts.
It is clear from the above discussion that every medicinal and food substance follows its own characteristic dose response curve. Starting from a base level of 100, as the dose is increased, the overall health parameter increases. However, a peak is reached at some particular dose beyond which a further increase in the dose will lead to reduction in the benefit. If dose is increased even further, the overall health parameter will almost certainly go below the initial level of 100 i.e. turn negative.
This response of dose on bioactivity is illustrated for a hypothetical herb in Table 1 below in the conventional and super-extract form.
Table 1: Effect of Dose on Bioactivity
|Daily Dose, mg||Super-extract||Conventional|
The concentration range at which the positive part of the curve will lie will definitely vary from one herbal source to the next. The sharpness of the dose response and the positive effect dose band will also vary from one substance to the next. The poisonous herbs will peak perhaps at a fraction of mg whereas adaptogens may peak at 5 to 10 gm level.
In Table I, the hypothetical dose response data for the same herb made into a super-extract is also shown. The peak in the beneficial effect is shifted to a dose which is several hundred times lower. However, the general features of a bell shaped curve are equally applicable to super-extracts as well. All it means is that the dose response curve is shifted to the left.
The same data is plotted in Figure 1 below.
As shown in this illustrative Figure, the useful activity for the conventional form has peaked at a dose of 100 mg / D whereas; the useful activity of the super-extract of the same herb has peaked at an herbal dose of 0.32 mg / D. Just as the conventional dose gives activity below 100 at doses above 320 mg / D, super-extract will also give activity below 100 at doses above 1 mg/day.
3. Super-Extracts Sensitivity: The super-extracts of any herb therefore may be as sensitive to side effects due to overdose as the herb given in conventional form.
The sensitivity of the super-extracts is expected to be similar to the conventional form on a logarithmic scale. Thus, if a conventional form has a useful range over a factor of 5 in dosage terms (e.g.1 to 5 gm / D), the super-extract is also expected to have a useful range over a 5 fold range off concentration (e.g. 3 to 15 mg / D).
This point needs to be clearly understood and large excess of super-extracts must be avoided.