More Liver

It's time to celebrate your liver. It's a hard-working organ and it deserves some credit.

One of the liver's most important overall functions is maintaining nutrient homeostasis. It controls the blood level of a number of macro- and micronutrients, and attempts to keep them all at optimal levels.

Here's a list of some of the liver's functions I'm aware of:

• Buffers blood glucose by taking it up or releasing it when needed
• A major storage site for glycogen (a glucose polymer)
  
• Clears insulin from the blood
• Synthesizes triglycerides
• Secretes and absorbs lipoprotein particles ("cholesterol")
• Stores important vitamins: B12, folate, A, D, E, K (that's why it's so nutritious to eat!)
• Stores minerals: copper and iron
  
• Detoxifies the blood
• Produces ketone bodies when glucose is running low
• Secretes blood proteins
• Secretes bile
• Converts thyroid hormones
• Converts vitamin D (D3 --> 25(OH)D3)
  

The liver is an all-purpose metabolic powerhouse and storage depot. In the next post, I'll give you a recipe for it...

The Liver: Your Metabolic Gatekeeper

As I've been learning more about the different blood markers of metabolic dysfunction, something suddenly occurred to me. Most of them reflect liver function! Elevated fasting glucose, low HDL cholesterol, high LDL cholesterol, high triglycerides and high fasting insulin all reflect (at least in part) liver function. The liver is the "Grand Central Station" of cholesterol and fatty acid metabolism, to quote Philip A. Wood from How Fat Works. It's also critical for insulin and glucose control, as I'll explain shortly. When we look at our blood lipid profile, fasting glucose, or insulin, what we're seeing is largely a snapshot of our liver function. Does no one talk about this or am I just late to the party here?!

I read a paper today from the lab of C. Ronald Kahn that really drove home the point. They created a liver-specific insulin receptor knockout (LIRKO) mouse, which is a model of severe insulin resistance in the liver. The mouse ends up developing severe whole-body insulin resistance, dramatically elevated post-meal insulin levels (20-fold!), impaired glucose tolerance, and elevated post-meal and fasting glucose. Keep in mind that this all resulted from nothing more than an insulin resistant liver.

LIRKO mice had elevated post-meal blood glucose due to the liver's unresponsiveness to insulin's command to take up sugar. Apparently the liver can dispose of one third of the glucose from a meal, turning it into glycogen and triglycerides. The elevated fasting glucose was caused by insulin not suppressing gluconeogenesis (glucose synthesis) by the liver. In other words, the liver has no way to know that there's already enough glucose in the blood so it keeps on pumping it out. This is highly relevant to diabetics because fasting hyperglycemia comes mostly from increased glucose output by the liver. This can be due to liver insulin resistance or insufficient insulin production by the pancreas.

One of the interesting things about LIRKO mice is their dramatically elevated insulin level. Their pancreases are enlarged and swollen with insulin. It's as if the pancreas is screaming at the body to pick up the slack and take up the post-meal glucose the liver isn't disposing of. The elevated insulin isn't just due to increased output by the pancreas, however. It's also due to decreased disposal by the liver. According to the paper, the liver is responsible for 75% of insulin clearance from the blood in mice. The hyperinsulinemia they observed was both due to increased secretion and decreased clearance. Interestingly, they noted no decline in beta cell (the cells that secrete insulin) function even under such a high load.

Something that's interesting to note about these mice is they have very low blood triglyceride. It makes sense since insulin is what tells the liver to produce it. Could this have something to do with their lack of beta cell dysfunction?

The really strange thing about LIRKO mice is that their blood glucose becomes more normal with age. Strange until you see the reason: their livers are degenerating so they can't keep up glucose production!

LIRKO mice reproduce many of the characteristics of type II diabetes, without degenerating completely into beta cell death. So insulin resistance in the liver appears to reproduce some elements of diabetes and the metabolic syndrome, but the full-blown disorders require other tissues as well. As a side note, this group also has a skeletal muscle-specific insulin receptor knockout which is basically normal. Interesting considering muscle tissue seems to be one of the first tissues to become insulin resistant during diabetes onset.

So if you want to end up like your good pal LIRKO, remember to drink high-fructose corn syrup with every meal! You'll have fatty liver and insulin resistance in no time!

I have a lot more to say about the liver, but I'll continue it in another post.

Book Review: Blood Sugar 101

I just finished reading "Blood Sugar 101" by Jenny Ruhl. It's a quick read, and very informative. Ruhl is a diabetic who has taken treatment into her own hands, using the scientific literature and her blood glucose monitor to understand blood sugar control and its relationship to health. The book challenges some commonly held ideas about diabetes, such as the notion that diabetics always deteriorate.

She begins by explaining in detail how blood glucose is controlled by the body. The pancreas releases basal amounts of insulin to make glucose available to tissues between meals. It also releases insulin in response to carbohydrate intake (primarily) in two bursts, phase I and phase II. Phase I is a rapid response that causes tissues to absorb most of the glucose from a meal, and is released in proportion to the amount of carbohydrate in preceding meals. Phase II cleans up what's left.

In a person with a healthy pancreas, insulin secretion will keep blood glucose under about 130 mg/dL even under a heavy carbohydrate load. The implications of this are really interesting. Namely, that blood glucose levels will not be very different between a person who eats little carbohydrate, and one who eats a lot, as long as the latter has a burly pancreas and insulin-sensitive tissues.

Most Americans don't have such good control however, hence the usefulness of low-carbohydrate diets. This begs the question of why we lose blood sugar control. Insulin resistance seems like a good candidate, maybe preceded by leptin resistance. As you may have noticed, I'm starting to think the carbohydrate per se is not the primary insult. It's probably something else about the diet or lifestyle that causes carbohydrate insensitivity. Grain lectins are a good candidate in my opinion, as well as inactivity.

Diabetics can have blood glucose up to 500 mg/dL, that remains elevated long after it would have returned to baseline in a healthy person. Ruhl asserts that elevated blood sugar is toxic, and causes not only diabetic complications but perhaps also cancer and heart disease.

Heart attack incidence is strongly associated with A1C level, which is a rough measure of average blood sugar over the past couple of months. It makes sense, although most of the data she cites is correlative. They might have seen the same relationship if they had compared heart attack risk to fasting insulin level or insulin resistance. It's difficult to nail down blood sugar as the causative agent. More information from animal studies would have been helpful.

Probably the most important thing I took from the book is that the first thing to deteriorate is glucose tolerance, or the ability to pack post-meal glucose into the tissues. It's often a result of insulin resistance, although autoimmune processes seem to be a factor for some people. Doctors often use fasting glucose to diagnose diabetes and pre-diabetes, but typically you are far gone by the time your fasting glucose is elevated!

I like that she advocates a low-carbohydrate diet for diabetics, and lambasts the ADA for its continued support of high-carbohydrate diets.

Overall, a good book. I recommend it!

Olive Oil Buyer's Guide

Olive oil is one of the few good vegetable oils. It is about 10% omega-6 (n-6) fatty acids, compared to 50% for soybean oil, 52% for cottonseed oil and 54% for corn oil. Omega-6 fatty acids made up a smaller proportion of calories before modern times, due to their scarcity in animal fats. Beef suet is 2% n-6, butter is 3% and lard is 10%. Many people believe that excess n-6 fat is a contributing factor to chronic disease, due to its effect on inflammatory prostaglandins. I'm reserving my opinion on n-6 fats until I see more data, but I do think it's worth noting the association of increased vegetable oil consumption with declining health in the US.

Olive oil is also one of the few oils that require no harsh processing to extract. As a matter of fact, all you have to do is squeeze the olives and collect the oil. Other oils that can be extracted with minimal processing are red palm oil (9% n-6), hazelnut oil (10% n-6) and coconut oil (2% n-6). These are also the oils I consider to be healthy. Due to the mild processing these oils undergo, they retain their natural vitamin and antioxidant content.

You've eaten corn, so you know it's not an oily seed. Same with soybeans. So how to they get the oil out of them? They use a combination of heat and petroleum solvents. Then, they chemically bleach and deodorize the oil, and sometimes partially hydrogenate it to make it more shelf-stable. Hungry yet? This is true of all the common colorless oils, and anything labeled "vegetable oil".

Olive oil is great, but don't run out and buy it just yet! There are different grades, and it's important to know the difference between them. The highest grade is extra-virgin olive oil, and it's the only one I recommend. It's the only grade that's not heated or chemically refined in any way. Virgin olive oil, "light" olive oil (refers to the flavor, not calories), "pure" olive oil, or simply olive oil all involve different degrees of chemical extraction and/or processing. This applies primarily to Europe. Unfortunately, the US is not part of the International Olive Oil Council (IOOC), which regulates oil quality and labeling.

The olive oil market is plagued by corruption. Much of the oil exported from Italy is cut with cheaper oils such as colza. Most "Italian olive oil" is actually produced in North Africa and bottled in Italy, and may be of inferior quality. The USDA has refused to regulate the market so they get away with it. If you find a deal on olive oil that looks too good to be true, it probably is.

Only buy from reputable sources. Look for the IOOC seal, which guarantees purity, provenance and freshness. IOOC olive oil must contain less than 0.8% acidity. Acidity refers to the percentage of free fatty acids (as opposed to those bound in triglycerides), a measure of damage to the oil. Fortunately, the US has a private equivalent to the IOOC, the California Olive Oil Council (COOC). The COOC seal ensures provenance, purity and freshness just like the IOOC seal. It has outdone the IOOC in requiring less than 0.5% acidity. COOC-certified oils are more expensive, but you know exactly what you're getting.

Thanks to funadium for the CC photo

Real Food V: Sauerkraut

Sauerkraut is part of a tradition of fermented foods that reaches far into human prehistory. Fermentation is a means of preserving food while also increasing its nutritional value. It increases digestibility and provides us with beneficial bacteria, especially those that produce lactic acid. Raw sauerkraut is a potent digestive aid, probably the reason it's traditionally eaten with heavy food.

Sauerkraut is produced by a process called ‘anaerobic’ fermentation, meaning ‘without oxygen’. It’s very simple to achieve in practice. You simply submerge the cabbage in a brine of its own juices and allow the naturally present bacteria to break down the sugars it contains. The process of ‘lacto-fermentation’ converts the sugars to lactic acid, making it tart. The combination of salt, anaerobic conditions, and acidity makes it very difficult for anything to survive besides the beneficial bacteria, so contamination is rare. If it does become contaminated, your nose will tell you as soon as you taste it.

Store-bought sauerkraut is far inferior to homemade. It's soggy and sterile. Ask a German: unpasteurized kraut is light, crunchy and tart!

My method is inexpensive and requires no special equipment. I've tested it many times and have never been disappointed.

Materials

• Wide-mouth quart canning jars (cheap at your local grocery store)
• Beer bottles with the labels removed, or small jars that fit inside the canning jars
• Three tablespoons of sea salt (NOT iodized table salt-- it's fatal to our bacteria)
• Five pounds of green cabbage

Recipe

1. Chop cabbage thinly. Ideally the slices should be 2 mm or so wide, but it doesn’t matter very much. You can use a food processor, mandolin or knife.
2. Put all the cabbage together in a large bowl and add the salt. If the salt is not very dense (sometimes finely ground sea salt can be fluffy), you can add up to 5 tablespoons total. Mix it around with your hands. Taste some. It should be good and salty.
3. Let the salted cabbage sit in the bowl for 30 minutes or so. It should be starting to get juicy.
4. Pack the cabbage tightly into the canning jars. Leave 2-3 inches at the top of the jar. When you push on the cabbage in the jar, you should be able to get the brine to rise above the cabbage. Try to get rid of air bubbles.
5. Put water into the beer bottles and place them into the canning jars. The weight of the bottles will keep the cabbage under the brine. It’s okay that some of the brine is exposed to the air; the cabbage itself is protected.
6. Let it sit for 2 weeks at room temperature! As the fermentation proceeds, bubbles will form and this will raise the level of the brine. This is normal. You might get some scum on top of the liquid; just check for this and scrape it off every few days. It won’t affect the final product. If the brine drops to the level of the cabbage, add salt water (1 tsp/cup, non-chlorinated water) to bring it back up.
7. Taste it! It should be tart and slightly crunchy, with a fresh lactic acid flavor. If fully fermented, it will keep in the fridge for a long time.

Here are some photos from making sauerruben, which is like sauerkraut but made with turnips: