I was asked recently whether alpha-lipoic-acid might help neuropathy in the feet. The research showed that it did but that the improvement is temporary, about 3 – 7 months. Since neuropathy is common in diabetes and diabetes is a model of an inability to burn glucose for nutrient support, I supposed that neuropathy in non-diabetics is a model of ineffective metabolism that burns mostly fatty acids because it can no longer use glucose at a fast enough rate to prevent nerve impairment, even without a diabetic diagnosis.
Because diabetics are more vulnerable to cancer than non-diabetics it seems clear to me that not supplying the metabolism with glucose by not eating dense carbs, eating polyunsaturated fats, forcing the body into burning fatty acids is dangerous even though the cultural messaging is exactly the opposite, especially in the medical community. It is risky the same way radon in the basement or arsenic in well water is: everyone seems to think its harmless while the damage is beginning when it can most easily be changed.
These views of metabolism, the need for nutrient abundance through protective compensation of stress, generous supplies of readily usable energy substrate, light, and possibly a thyroid supplement to encourage a fuller use of glucose are not new. But in an environment of misunderstanding of how to see the whole organism’s role in degeneration and aging and the overwhelming ideological biases that keep this view hidden I think it’s worthwhile to talk about how this view works.
Should I take alpha-lipoic-acid for Neuropathy in my feet?
Should I take alpha-lipoic-acid for neuropathy that causes me to fall spontaneously? The basic answers to this question are yes, no, and some context. Thinking about this I wondered about how to say that a stress metabolism leads to degenerative symptoms like neuropathy and how eating dense carbs and eliminating PUFA would support reversal of the symptoms.
Here are all the preliminary questions you'd ever need to investigate first. They are common sense and can be skipped if you understand the principle of using them.
First, way too many questions:
1. Are you diabetic? Diabetes is always the model for neuropathy because diabetes is basically a wasting disease where tissues don’t get enough glucose to function fully. You might not be diabetic, but your tissues can suffer impaired function from impaired nutrient support, basically, inflammation. That can be neuropathy in the absence of clinical diabetes but it will be similar to a diabetic metabolism.
2. When is your neuropathy worse? For example, in the morning or at night? Summer or winter? Day or night? Cloudy weather or sunny days?
3. Can you exclude neuropathy being caused by nerve impingement coming from the spine? These answers can indicate that neuropathy is secondary to something else.
4. Other things to think about: What is your daily average calorie intake and what are the usual macros? How is your thyroid status? The whole context of your life that gives a picture of how you fit in your environment could be helpful to understanding symptoms. The constraints of time and attention are the limits. That’s where your involvement takes over from any advice anyone might give you.
Answers
The basic answers to whether to use ALA for this:
Yes, you should take alpha-lipoic-acid for mild neuropathy because some research shows evidence of improvement in symptoms and performance [nerve function testing] with ALA. Note, in case you are googling: “ALA” also frequently is used to stand for alpha-linoleic-acid and alpha-linolenic-acid. These are types of omega -3s and not the same thing as alpha-lipoic-acid.
Most of the positive evidence comes from a 1999 German study [https://www.ncbi.nlm.nih.gov/pubmed/10595592 abstract only]. This study was limited to positive results in diabetic neuropathy with I.V. administration of ALA over 3 weeks at 600mg/day. Follow-up studies reported in that abstract include 6-weeks of oral doses at 1800 mg/day with no conclusive results. Much of the popular media about positive results seems to come from this study.
By 2011 there was a meta-data study [a study of studies] done to evaluate ALA for this use up to that time [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176171/.] The studies that were collapsed and reported here ranged from very small numbers [24 diabetics] to higher [384] for a total number of 1160 diabetics in 5 studies.
In general the outcomes looked like this:
a) I.V. administration showed the best improvement but were of short duration [2 – 5 weeks];
b) I.V. [short-term] with oral follow-up [3 – 7 months] showed initial improvement that dropped off to zero after about 3 months;
c) oral administration studies were short [2 – 5 weeks] but showed improvement that was greater with higher dosages but with more subject drop-outs because of side-effects [headache, nausea, vomiting], a whopping 54% at 1800mg/day.
What is ALA?:
ALA is an anti-oxidant, is excreted by the kidneys, and is only about 30% absorbed in the gut. Its absorption is worse with food so take on an empty stomach. With that rate of absorption and the reported GI side-effects, it might be just as useful to open a capsule and rub it on your feet.
ALA exists in tiny amounts in spinach, broccoli, yams, potatoes, nutritional yeast, tomatoes, Brussels sprouts, carrots, beets, rice bran, and red meat. But getting ALA from these foods isn’t practical. It can be produced by the body. In general, young bodies produce more than older bodies.
A general explanation for why ALA helps neuropathy:
ALA is an anti-oxidant that can apparently contribute enzymatic support to the production of energy when the mitochondria cannot completely metabolize glucose because the body is experiencing physiological stress [starvation, famine, dieting, insomnia, emotional upset, drugs, accidents, trauma, winter, night, demanding work, over-exercising, poverty, war] and so it tends to work less effectively, sometimes initially described as metabolic insufficiency. The human organism is sensitive to stress and quickly uses its glucose and then partly switches to a slower metabolic pathway that conserves energy by making it at a slower rate. But the switch comes at the cost of catabolism of functions and tissues. In this context neuropathy is a result of metabolic stress.
If the body were more metabolically efficient in using glucose, then it wouldn’t have neuropathy. The neuropathy in turn becomes a stress that perpetuates poor nerve metabolic support. If ALA helps neuropathy, then it is likely contributing to nerve cells getting the nutrient support they need for full functioning.
Metabolism and non-diabetic neuropathy:
Under even minor stress the body uses glucose massively. Older bodies usually don’t store as much glycogen as younger bodies. The body stores about 500 grams of glycogen. Marathon runners deplete glycogen in about 1.5 hours. When the body runs out of glycogen running a marathon, dieting, or sleeping without food for 8 or more hours it shifts to an alternate pathway of producing energy. This is a process of fermentation called glycolysis.
This type of anaerobic lactate formation is aided by the oxidation of fatty acids and tends to cut off the production of CO2 from glucose in the electron transport chain in the mitochondria, also called “oxphos,” “mitochondrial oxidation,” “mitochondrial respiration.” It can happen when oxygen is not present but it can also happen when oxygen is present but unable to be used because the loss of CO2 lessens the affinity of oxygen for the metabolic chain reaction. The metabolic physiology slows down, meaning ATP is formed at a slower rate.
The body physiologically cringes at stress.
When you exert yourself, work, or play your energy has to come from somewhere. If you are not supplying the body with glucose, then the body will make it out of body tissues, muscles, organs, even bone. This is why meth addicts have bad skin and teeth. They are producing movement without supplying enough fuel to do it with so their tissues become cannibalized. In a frantic world it’s hard to do enough to meet economic, social, health demands. Under the influence of economic culture the meaning of health gets transformed and assigned to people who look conventionally good while producing a lot.
In metabolic stress glycolysis produces lactic acid as a basic material for energy. You might sense when this has been happening because you will have sore, stiff muscles, there will be a tendency to gain fat, and there may be fatigue. When this happens because of exercise that has exceeded the body’s capacity to provide fuel you can recover quickly. But exercise-induced glycolysis is a model for chronic glycolysis that happens because there is not enough glucose available to produce energy when you are not exercising. Or, there is glucose but the cells can’t use it. With enough time the body can become accustomed to this and we call the accompanying adaptations, “just getting older.” Or, over certain clinical numbers, is called "Type 2 Diabetes."
No one has been able to demonstrate at the cellular level why ALA helps neuropathy symptoms. Medicine blames chronic hyperglycemia [lack of diabetic control] and insulin resistance but this is just another way to say that the condition called diabetes is often accompanied by neuropathy. In this view the nerves don’t get enough glucose to function and ALA apparently aids glucose uptake. It has been shown to lower blood glucose so the glucose is going into the nerve cells.
If a person is not diabetic, the results of using ALA for neuropathy might still be good to the extent that the body uses glycolysis for energy production. The ALA could help drive slightly better glucose uptake as long as glucose is available. The body probably always uses some glycolysis sometimes in some tissues but it is especially generalized when you have low blood sugar, before breakfast, when fasting, when ill or stressed, exercised away glycogen stores, are on a diet and losing fat, or are hypothyroid.
Another answer:
No, you should not take alpha-lipoic-acid for mild neuropathy because the neuropathy isn’t being caused by an ALA deficiency but by an excess of anaerobic glycolysis, one way the body produces energy under conditions of metabolic stress. ALA supplementation can and probably will help but not for the long-term. The problem is really elsewhere and generally metabolic.
The real problem is chronic glycolysis and the body’s incapacity to use oxygen to metabolize glucose all the way down to CO2 and water.
ALA will help but only until the body adapts as far as it can to the effects of the ALA, then it stops working. This adaptation appears to take about 3 months. The good news is ALA will help. The bad news is that it will help because the metabolism is using glycolysis enough that it is interfering with the production or complete use of glucose enough that nerves in the feet are not getting nutrients for full function. Not enough energy is being produced in the time needed to fuel the demands on the nerves.
The real answer:
The real answer in this wider context is to get the body to more completely metabolize glucose and rely less on glycolysis. It would be hard to rehabilitate and train the body to burn glucose and not cannibalize its tissues without eating a significant amount of dense carbs. Even emergency medicine uses glucose and hypertonic saline to control the stress of shock. If physiological stress is like sub-clinical shock, then eating sugar and adding salt to taste would control cortisol and adrenaline, the mediators of catabolic processes.
Rehabilitating the metabolism is a longer project than taking a supplement. But how long it takes is indicative of how much the body has adapted to a stress metabolism.
You could take ALA while you are rehabilitating your tissues to produce more energy from glucose.
Contextualizing neuropathy and metabolism:
The glycolytic metabolism uses massive amounts of glucose as fuel [made from fatty acids or other tissues] but will not burn it completely to CO2 and water. With a mostly glycolytic metabolism the body isn’t producing energy as fast as it could by burning glucose and it doesn’t produce and retain as much CO2 as it could. It is energetically expensive because some of the energy it produces has to be recycled to produce more. Glucose burning produces energy, CO2 and water.
It’s like people used to say about eating celery as a weight loss food: it takes more energy to chew it than it provides in nutrients. What they didn’t say was where the nutrients for chewing that celery would come from.
Cells don’t take up oxygen just because the lungs breathe more deeply, but by retaining CO2, which signals hemoglobin to release oxygen into the tissues and give it an affinity for mitochondrial respiration. If breathing deeper oxygenated tissues better then breathing in a paper bag wouldn’t stop anxious hyperventilation, but it does. Almost 2 generations of the promotion of aerobic exercise has obscured the general understanding of the role of CO2 retention in metabolic health. “Aerobic” exercise is often fueled by anaerobic glycolysis even when oxygen is present. An abundance of CO2 stabilizes proteins and makes oxygen usable.
Anti-sugar propaganda and “healthy” deep breathing advice do so much to drive real physiology down that it would be surprising if these 2 things were not the main drivers of bad health.
Cells need glucose and oxygen in order for mitochondrial respiration to work as fast as it can and to minimize glycolysis. In the special case of bone health it is already known that people who retain high levels of CO2 have denser bones. Most of the body’s CO2 is stored in the bones. People living at high altitude have slightly higher average bone mass than people living at sea level.
On bone health and neuropathy, one view is that abnormal calcium homeostasis affects neuropathy at the cellular level [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834846/ for example]. Too much calcium inside cells changes the balance of H2O in tissues and binds oxygen that would otherwise be used to break down glucose.
Anaerobic glycolysis is a metabolic process that accumulates slowness in the body processes leading to degenerative problems of all kinds. Glucose burning accommodates quickness that is limited only by how fast the lungs can supply oxygen in response to CO2 and the blood can supply glucose. Glycolytic slowness creates more slowness where the limit is rigor mortis. Quickness creates more quickness where the limit is respiration rate in both the cells and the lungs.
With neuropathy the nerve cells would need a steady supply of adequate glucose and oxygen in order to function fully without wasting energy in glycolysis and urging the body to adapt to a slow, low-oxygen, swollen state. Swollen nerves just can’t function fully.
What to do in this view:
To avoid the progressive slowing and degenerative processes it would be good to supply the body with enough dense carbs to prevent low blood sugar, loss of glycogen, adrenaline, cortisol, and anaerobic glycolysis as the main energy pathway. The goal would be robust and steady blood sugar and not just remedying low blood sugar once it has started.
A ready supply of glucose and enough CO2 are the drivers of mitochondrial respiration. It is the need for CO2 that links the respiration of the lungs by means of the circulation of oxygen and nutrients to the respiration of mitochondria in cells in every tissue of the body.
Should you supply the body with ready sources of glucose by eating sugar? The answer to this is heavily culturally biased by the idea that “sugar is addictive” the way you might say, “amphetamines are addictive” when you really mean, “oxygen is addictive.”
You would want the body to be able to store glycogen, which wouldn’t be possible without eating a lot of dense carbs. The readiest source of this is sugar whether it’s fruit or even table sugar. Without glycogen stores the body produces adrenaline and cortisol to maintain blood sugar it makes from tissues. Cushing’s syndrome is the model of chronic high cortisol along with fat gain, high blood pressure, and insulin resistance. The degenerative symptoms of “old age” are like a little Cushing’s.
De-adapting and re-adapting the body to robust mitochondrial respiration could take some time and patience though supplying the right nutrients at the right time in the right proportions could give very quick results. Eating dense carbs isn’t the whole story, but it is a key point in supplying glucose. Even 300g of carbs daily would be helpful for a working or healing body. You’d also need at least 80 – 125g of protein and some fat daily.
Keeping calories as high as possible without gaining too much fat would be a good way of thinking about nutrition. Today it isn’t uncommon for people to think that 1200 calories a day is adequate even though the Minnesota Semi-starvation experiments in 1944 used 1700 calories per day as the low rations for young men.
Another answer is not to eat any sugar [dense carbs, table sugar, fruit, etc.] so that the body will use all of the available glucose and stored glycogen and then use fat. In fact it does both at the same time, but for illustration let’s just say glucose-burning, then fat-burning. Many people report losing fat on high fat, low carb diets, inducing ketosis. The body can run on ketones, even your brain can run on ketones under conditions of famine and starvation. It is a resourceful energy hog.
Running on ketones is not dangerous but the ketones have to come from somewhere. The conversion of fat to ketones by means of glycolysis and fatty acid oxidation does drive down the speed of metabolic processes over time and the tissue loss destabilizes the whole organism. Especially when the fat is substantially PUFA. The recognition that PUFA are dangerous to metabolic functions is now being recognized more widely. The danger is its downstream oxidative by-products and its removal of enzymes from metabolic chemical chain reactions. Those enzymes then can’t be used even for glycolysis.
The people who lose a lot of fat on keto are effectively choosing between the dangers of storing high-PUFA fat versus the downstream effects of burning PUFA. “Re-feeding” periodically can somewhat spare the worst effects of burning it. But ketosis still requires adrenaline and cortisol and slows the body processes over time. The problem is not the ketosis itself but the stress hormones produced in order to do it, which cannibalize muscle and organ tissue as well as fat.
The good news is the body can also make glucose. The bad news is it makes glucose out of fat or protein. The protein source for your body making glucose is muscle tissue. In this case you might know this has been happening when you work hard in the gym, think you are eating enough, but don’t build the muscle you expect to build. Without energy from carbs even lifting weights could contribute to sarcopenia. Your fasting glucose might creep up a bit over time.
But the body is promiscuous about what tissues it will metabolize for energy. Or it seems that way because we don’t know exactly how it chooses which tissues to cannibalize first. Herein is the beginning of adaptive, degenerative diseases. Nerve function might be peripheral enough that it deteriorates for lack of nutrients, ready glucose. When the body has to sacrifice tissue or function it often does this in the extremities first in order to conserve the essential functions of heart, lungs, brain, liver, kidneys.
If the neuropathy gets worse then the most often prescribed medical solutions are GABA agonists [Lyrica], antidepressants [Cymbalta], and sometimes opioids for pain. These can bring some perceived relief without changing the conditions causing the neuropathy or even making them worse in the long run. Like ALA, the treatment is a way of adapting to an inflammatory state.
Eat enough sugar and don’t hyperventilate oxygen.
Things that help are having enough dense carbs in the diet, at least twice as many grams of carbs as of protein to supply the energy needed to metabolize the protein. Eliminating PUFA from the diet. Adequate salt to lower adrenaline and cortisol, which is catabolic to tissues. Keeping blood sugar stable and adequately high through the day. Taking carbs at night if you wake up because of low blood sugar. Using T3 thyroid, progesterone, minimizing estrogen, serotonin, histamine.
If you can’t be at high altitude then supplying CO2 simply by breathing in a bag a few times a day can relax blood vessels, oxygenate the tissues and brain, lower anxiety, and slightly help the cells expel calcium, which is needed in the bones rather than the tissues. Applying a lidocaine cream [Aspercreme lidocaine] can de-habituate the nerves while you sort ways to improve metabolism.
In general, until inflammatory states are viewed as adaptations to stress and the body reverting to glycolytic metabolism, degenerative symptoms more likely will be treated as mysteriously caused and not able to be compensated. In the meantime, the problems of degenerative disease and the potential of simple dietary changes that happen to go against cultural biases to reverse this are inexpensive, available, and safe.
©Celise Schneider 2018
photo credit: Pineapple Supply Co. pexels.com
http://raypeat.com/articles/articles/sugar-issues.shtml Ray Peat article on the role of sugar and fatty acid metabolism in diabetes.
http://raypeat.com/articles/ A source for the whole organism view of health, compensation of stress, reasons for degeneration, history of this view, and suggestions for how to think rationally about about health and the politics of health.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834846/ Abnormal Calcium Homeostasis in Peripheral Neuropathies, Paul Fernyhough and Nigel A. Calcutt (2011) The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies.