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Artificial sweeteners are incredibly popular and the reason is simple: they
seem like a fantasy, almost too good to be true. Take the case of
saccharin: it is about three hundred times as sweet as sugar and yet is
zero calories. That's the allure: we get all the sweetness that we want
with no metabolic or weight gain consequences.
Unfortunately, the picture is not so simple. Artificial sweeteners are not
just a little artificial - they are very artifical and produce some very
surprising (negative) effect, which we will cover below for each sweetener.
However, one thing that should be realized is that all artificial sweeteners will
likely cause your problems and have been
associated with obesity. In fact,
one study found that regular consumers of artificial sweeteners, in this case
saccharin, had their brain's reward system to sweets altered. Basically,
regular consumers of diet beverages responded more strongly to sweets, thus
making them more vulnerable to overconsumption and, eventually, weight gain.
NEWS FLASH: One recent study found cancer-causing properties associated with
aspartame and saccharin, two of the three sweeteners discussed below. 
Let's start with the three most popular on the market
Aspartame, Equal or Nutrasweet
This sweetener is almost synonymous with the word "diet" and is ubiquitous in diet drinks,
including Diet Coke and Diet Pepsi. It is consumed in vast quantities by people
around the globe and so it has to be safe, right? Unfortunately, nothing could
be further from the truth.
If you haven't heard, aspartame is quickly metabolized by the
body and broken down into some nasty chemicals, including methanol, formaldehyde
and aspartate. The ensuing chemical soup is already linked to a variety of very serious conditions
in both animal and human studies:
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1. Excitotoxin Syndrome. This is a reversible but debilitating
condition linked to the nasty excitotoxin, aspartate, that is metabolized from Aspartame. You can
read more here in my link on Excitotoxin Syndrome.
I don't know anyone who drinks more than, say, three Diet Cokes or Diet Pepsis
that does not struggle with many of these symptoms.
Lymphoma and Leukemia. One animal study in a prestigious European journal
already found "a statistically significant, dose-related increase in lymphomas
and leukaemias in females" at about the equivalent level of three diet sodas per
day.  This study was conducted on 1,800 rats and the control animals had no
lymphomas. In contrast, the animals consuming aspartame had 10 malignant gliomas, 1
medulloblastoma and 1 malignant meningioma!
3. Kidney Decline. Kidney decline is nasty, serious business
(likely from the
formaldehyde metabolized from aspartame) has now been linked to this condition
in a study of nurses.  Read
more here at this link in the News Flash on the bottom of this page on
4. Testosterone and Reproduction. Numerous animal studies show that fetal
excitotoxin exposure - excitotoxins pass rather easily through the placental
barrier - can lead to reproductive and hormonal difficulties later in
life. Read here about how
Excitotoxins Can Decrease Testosterone. This may
be an issue for us humans later in life, because cell phone and
exposure likely weaken our blood-brain barrier later in life.
(Excitotoxins also go largely unimpeded into the hypothlamus where they can do
considerable damage as well.)
Saccharin or Sweet 'n Low
Supposedly, the story of saccharin is like the story of death row inmates who are
found later to be innocent and then freed upon the public at large.
Many people, health conscious or not, know about how saccharin was implicated as
a cause of bladder cancer in a famous rat studies of 1977-1980. 
However, it didn't take long for several flaws in the study to come out,
including the fact that fat metabolism is different and the dosage was much,
much beyond any reasonable amount that could be consumed by a human.
Now the pendulum has swung back in the other direction and many consider
saccharin the safest of the artificial sweeteners. I would argue caution
for the following reason:
1. Liver Irritation and Toxicity. Saccharin can be hard on the
and is known for increasing aminotransferase levels, a sign of liver damage. One
study on rats showed no liver cancer when saccharin alone was given to rats.
However, when another liver-cancer causing agent was administred, saccharin
greatly accelerated the rate of cancer. 
In other words, saccharin may simply accelerate any underlying liver problems, a
very serious problem indeed in our day of chemicals and drugs, which often
overtax our livers. (In fairness, another similar study found no
such toxicity. )
It should be noted, also, that one study showed DNA modifications from
saccharin in mice. 
Sucralose or Splenda
So far sucralose has avoided the spotlight as far as negative press and
deservedly so: it has had, as far as I know, only one valid negative study to
date: one set of researchers found that it negatively effected intestinal flora
and pH. 
If true, this is a very serious charge indeed as "gut flora", one's good
intestinal bacteria, is critical for immune function and some digestive
processes. Plus, the animals gained weight.
However, more work is needed as this study has received some
criticism for being insufficiently rigorous.
One last note: sucralose has been cited by Medscape
as a possible migraine trigger in sensitive individuals:  This has not been verified, however, by a
formal study nor do researchers know of any mechanism by which this might occur.
CAUTION: A lot of health-conscious people are running to Stevia and
Agave as natural alternatives to sugar and alternative sweeteners. Yes, they are
natural in the sense that they have been consumed as foods. The agave
plant is grown in Mexico and is touted as a "low glycemic"
problem is that it is relatively non-sweet in taste and, I just learned,
very high (92%) in fructose.  In other words, it would be very easy to pack on the
pounds with agave syrup. Furthermore, agave syrup does not contain
fructose and the percentage goes up each year with increasingly modern
manufacturing techniques that use higher and higher heat. One study
on Stevia should give most guys pause: higher doses have led
to decreases in testosterone and reduced sperm
counts in laboratory animals. 
1) Eur J Oncol, 2005, (10)(2):00-00
2) Cancer Res, Mar 1980, 40:734-736 ,"Saccharin-induced hyperplasia of the Rat
3) New Eng J of Med, July 14 1994, 331:134-135, "The Hepatotoxicity of Saccharin"
4) Envir Health Perspectives, 1983, 50:169-176, "Effect of DibutyInitrosamine and
Saccharin on Glutamyl Transpeptidase-Positive Foci and Liver Cancer"
5) Toxicological Sciences, Received March 28, 1988; accepted July 12, 1988,
12(2): 346-357, "The Effect of Lifetime Sodium Saccharin Dosing on Mice
Initiated with the Carcinogen 2=Acetylaminofluorere"
6) Boll Soc Ital Biol Sper, Dec 15 1980, 56(23):2486-2491,
"Renal and hapatic toxicity studies in mice treated with sodium
saccharin: breaks in single-stranded DNA"
7) J of Toxicology and Envir Health, Part A, Jan 2008, 71(21): 1415-1429,
"Splenda Alters Gut Microflora and Increases Intestinal P-Blycoprotein and
Cytochrome P-450 in Male Rats"
8) Drug and Chemical Toxicity, 2008, 31(4):447-457,
"Genotoxicity Testing of Low-Calories Sweeteners:
Aspartame, Aesulfame-K and Saccharin"
10) Journal of Ethnopharmacology, Nov 1999, 67(2):157-161, Received 30 November
1998;revised 22 December 1998;accepted 24 December 1998.Available online 10
September 1999., "Effects of chronic administration of Stevia rebaudiana on
fertility in rats"
13) Physiology & Behavior, Available online 11 May 2012, "Altered processing of
sweet taste in the brain of diet soda drinkers"